Abstract / Summary
Alopecia areata (AA) is an autoimmune disease affecting approximately 2.1% of the population. JAK inhibitors represent a therapeutic breakthrough for severe AA, yet objective tools for monitoring treatment response remain limited. The objective of this study was to correlate trichoscopic and reflectance confocal microscopy (RCM) features with clinical changes in patients with severe AA treated with JAK inhibitors (upadacitinib and baricitinib) over 60 weeks. Twenty patients with severe AA were enrolled. Patients were treated with upadacitinib 15 mg/day or baricitinib 4 mg/day. Clinical (Severity of Alopecia Tool score), trichoscopic, and RCM evaluations were performed at baseline and every 12 weeks thereafter. Mean Severity of Alopecia Tool (SALT) decreased from 85% at baseline to 17% at week 60. Upadacitinib treated patients showed faster early response (32.6%% SALT reduction at week 12 vs. 5.2% increase with baricitinib), though both groups achieved comparable outcomes by week 60 (SALT 17%). Trichoscopy showed progressive reduction of activity markers: (yellow dots, black dots, broken hairs, and exclamation mark hairs) with characteristic regrowth sequence: short vellus hairs, upright regrowing hairs, terminal hairs. RCM identified three parameter categories: (1) inflammatory activity markers (epidermal infiltration, bright rimming, luminal bright material, cadaverised hairs), with persistent diffuse follicular inflammation and perifollicular muffle; (2) transient collagen remodelling features without fibrosis; and (3) recovery markers, including follicular normalisation (strongest RCM predictor of response) and vellus-to-terminal transition. JAK inhibitors demonstrated sustained efficacy in severe AA. Multimodal assessment combining SALT, trichoscopy, and RCM enables precise biological response monitoring. RCM uniquely detects subclinical perifollicular inflammation persisting despite clinical improvement, potentially predicting relapse risk after treatment discontinuation.